Biochemistry of heparin antithrombin interactions, and the physiologic role of this natural anticoagulant mechanism.

A small fraction of plasma antithrombin is normally bound to a specific population of heparan sulfate proteoglycans synthesized by macrovascular and microvascular endothelial cells. This permits the protease inhibitor to be selectively activated at blood-surface interfaces where enzymes of the intrinsic coagulation cascade are commonly generated. Thus, antithrombin is critically placed to neutralize these hemostatic enzymes and thereby protect natural surfaces against thrombus formation. Furthermore, the catalytic nature of this specific set of heparan sulfate proteoglycans ensures the continual regeneration of the nonthrombotic properties of the endothelial cell layer. Alterations in the synthesis and/or placement of the anticoagulantly active heparan sulfate proteoglycans on the surface of microvascular and macrovascular endothelial cells could be responsible for arterial and venous thrombotic disease in humans.